Osteoarthritis (OA) is characterized by progressive cartilage degradation accompanied by limited intrinsic repair capacity. Stromal vascular fraction (SVF) transplantation has demonstrated potential for regenerating damaged joint tissue; however, the pathological microenvironment impairs SVF stemness, thereby limiting therapeutic efficacy. Herein, we developed a bioinspired hydrogel formed via the cross-linking of hyaluronic acid-grafted dopamine and a fibroblast growth factor 2-mimetic peptide-modified RADA16-I. This injectable hydrogel combined excellent gelation performance with multifunctionality, particularly in enhancing SVF proliferation and chondrogenic differentiation. The hydrogel activated forkhead box M1 (FOXM1) - mediated epigenetic reprogramming, enhancing DNA repair capacity and increasing chromatin accessibility at pluripotency loci. In a rat OA model, combined hydrogel and SVF transplantation significantly enhanced articular cartilage regeneration and ameliorated OA symptoms. This study provides preliminary evidence showing that a biomaterial-mediated epigenetic reprogramming strategy improves recovery in OA, highlighting the therapeutic potential of the novel hydrogel for stem cell-based regenerative medicine.
Hou et al. (Mon,) studied this question.